Honokiol attenuates renal fibrosis via SIRT3-Mediated regulation of Wnt/β-Catenin signaling
- Funct Integr Genomics. 2026 Feb 10;26(1):42. doi: 10.1007/s10142-025-01816-6.
- 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, 430030, China.
- 2. Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Key Laboratory of Organ Transplantation, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Huazhong University of Science and Technology, Ministry of Education, Chinese Academy of Medical Sciences, Wuhan, China.
- 3. Department of Urology, Xijing Hospital, Air Force Medical University, Xi'an, China.
- 4. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, 430030, China. [email protected].
- # Contributed equally.
Renal fibrosis, a mutual pathological manifestation of chronic kidney disease (CKD), currently has limited therapeutic options. Honokiol (HKL), a polyphenolic compound isolated from Magnolia officinalis, has demonstrated anti-fibrotic effects; however, its molecular mechanisms remain incompletely characterized. The anti-fibrotic effect of HKL was investigated using the unilateral ureteral obstruction (UUO) mouse framework in vivo and transforming growth factor-β1 (TGF-β1)-stimulated HK2 cells in vitro, followed by HKL treatment and assessed by fibrosis markers and signalling axis. Conditional Sirtuin 3 (SIRT3) knockout (cKO) mice and SIRT3 siRNA-transfected HK2 cells were utilised to investigate the function of SIRT3 in mediating HKL’s anti-fibrotic impacts. HKL significantly attenuated renal fibrosis, reducing the deposition of extracellular matrix (ECM) and reversing epithelial-mesenchymal transition. Mechanistically, HKL-activated SIRT3 downregulated Wnt/β-catenin signaling axis, evidenced by decreased nuclear β-catenin accumulation and a subsequent reduction in transcriptional activity, which refers to the activation of fibrosis-related genetic factors like Collagen I, Fibronectin, and α-SMA upon β-catenin binding to TCF/LEF transcription factors. SIRT3 deficiency restored Wnt/β-catenin signaling axis activation and eliminated anti-fibrotic impacts of HKL. HKL mitigates renal fibrosis via SIRT3-mediated suppression of Wnt/β-catenin signaling, proposing a novel targeted therapeutic strategy for CKD-associated fibrosis.